Human immunodeficiency virus (HIV) causes acquired immune deficiency syndrome (AIDS) through infection of specialized cells of the immune system carrying CD4 receptors. The HIV retrovirus reproduces in these cells, especially the so-called T-helper cells, and kills them in the process. While the body has the ability to re-generate T-helper cells to some extent, after years of continuous cell destruction by HIV and fighting back by the immune system, the virus eventually emerges as the battle's winner. The progressive destruction of T-helper cells leads to weakening of the immune system which in turn, opens the door to opportunistic pathogens. When this happens, HIV-infected people start to show clinical symptoms. If left unchecked, HIV infection leads to death in a matter of years.
In order to reproduce in infected cells, HIV needs three major enzymes that are carried inside the viral particle. These three enzymes, reverse transcriptase, protease and integrase, thus represent ideal targets for antiviral therapy. Of these, reverse transcriptase has been the first enzyme targeted by the pharmaceutical industry. Inhibitors of the viral protease have been developed more recently and their use as drugs for AIDS treatment began only in 1996. Although the development of reverse transcriptase and protease inhibitors has improved significantly the survival time and quality of life of HIV-infected patients, their use leads to unwanted side effects, such as anemia, neurotoxicity, bone marrow suppression and lipodystrophy. Most of the currently available anti-protease drugs are large molecules with limited ability to cross the blood-brain barrier.
Some new compounds devoid of these drawbacks have been developed to treat HIV infections, and to fight the resistant viral strains. PCT International Patent Application no. PCT/CA02/00190 (Stranix et al.) published under No. WO 02/064551 HIV disclosed protease inhibitors based on amino acid derivatives. This patent application includes, more particularly, N-amino acid substituted L-lysine derivatives (and analogs) possessing aspartyl protease inhibitory properties. It was also provided some alternate compounds with such properties. For example, U.S. Pat. No. 6,632,816 B1 disclosed a novel class of aromatic derivatives possessing aspartyl protease inhibitory properties, and their biological applications in Treatment of HIV infections.
Long-acting antiretroviral agents are currently under development for the treatment of chronic HIV infection. Long-acting medications could offer an attractive option for people with HIV facing a lifetime of antiretroviral treatment. These agents have the advantage of being more convenient and potentially improving patient's adherence. However, none of previous studies provides a good long acting pharmaceutical composition of a protease inhibitor for treating HIV infection.